Many epidemiological studies implicate increased exposure to sunlight as a risk factor for cataract. Initial data argued that UVB light was the damaging element in sunlight, which was confirmed by animal studies. UVA light, while having no effect on rodent lenses, is increasingly being implicated in human cataract. This discrepancy arises from the fact that human lenses accumulate "yellow" protein modifications with aging, and these modified amino acids absorb UVA light. UVA light, which is completely absorbed by the human lens, has the potential to produce damaging oxygen free radicals. This is not a problem in young lenses due to the low oxygen content, but appears to be a significant damaging reaction in cataract lenses. There have been almost no investigations on the effects of UVA light on the lens constituents. Several candidate compounds will be analyzed for their ability to produce oxygen free radicals and for the oxidation of lens antioxidants. We have isolated and determined the structure of several novel "yellow" compounds from human lens. These compounds are photo-bleached by UVA light. The structure of the bleached compounds and the levels of these bleached compounds in human lens and cataracts will be determined. This will be a direct demonstration of UVA effects in lens tissue. Brunescent cataracts are characterized by intense browning and are a major cataract pathology tropical countries. This is likely due to an accumulation of tryptophan oxidation products in the lens proteins. Since we know that the tryptophan content of the lens is decreased in brunescent cataract, we will also determine the structure of the trp oxidation products in vitro by the UVA irradiation of human lens proteins. The content of these oxidation products will be analyzed in brunescent lenses from India to also document UVA damage in these lenses. Direct measurements of the various tryptophan oxidation products formed due to the exposure of lens proteins to singlet oxygen and to hydrogen peroxide will be made in order to identify which is the major damaging reactive oxygen species in brunescent cataract.